Tunnel Barrier Research Articles

Double-sided van der Waals epitaxy of topological insulators across an atomically thin membrane.

Atomically thin van der Waals (vdW) films provide a material platform for the epitaxial growth of quantum heterostructures. However, unlike the remote epitaxial growth of three-dimensional bulk crystals, the growth of two-dimensional material heterostructures across atomic layers has been limited due to the weak vdW interaction. Here we report the double-sided epitaxy of vdW layered materials through atomic membranes. We grow vdW topological insulators Sb2Te3 and Bi2Se3 by molecular-beam epitaxy on both surfaces of atomically thin graphene or hexagonal boron nitride, which serve as suspended two-dimensional vdW substrate layers. Both homo- and hetero-double-sided vdW topological insulator tunnel junctions are fabricated, with the atomically thin hexagonal boron nitride acting as a crystal-momentum-conserving tunnelling barrier with abrupt and epitaxial interfaces. By performing field-angle-dependent magneto-tunnelling spectroscopy on these devices, we reveal the energy-momentum-spin resonance of massless Dirac electrons tunnelling between helical Landau levels developed in the topological surface states at the interfaces.

Repurposing Linezolid in Conjunction with Histone Deacetylase Inhibitor Access in the Realm of Glioblastoma Therapies.

Since decades after temozolomide was approved, no effective drugs have been developed. Undoubtedly, blood-brain barrier (BBB) penetration is a severe issue that should be overcome in glioblastoma multiforme (GBM) drug development. In this research, we were inspired by linezolid through structural modification with several bioactive moieties to achieve the desired brain delivery. The results indicated that the histone deacetylase modification, referred to as compound 1, demonstrated promising cytotoxic effects in various brain tumor cell lines. Further comprehensive mechanism studies indicated that compound 1 induced acetylation, leading to DNA double-strand breaks, and induced the ubiquitination of RAD51, disrupting the DNA repair process. Furthermore, compound 1 also exhibited dramatic improvement in the orthotopic GBM mouse model, demonstrating its efficacy and satisfying BBB penetration. Therefore, the reported compound 1, provided with an independent therapeutic pathway, satisfying elongation in survival and tumor size reduction, and the ability to penetrate the BBB, was potent to achieve further development.

Development of Off-On Near-Infrared Fluorescent Probes for Sensitive In Vivo Imaging of Amyloid-β Species with Enhanced Pharmacokinetic.

The fluorescent imaging of pathologically accumulated β-amyloid (Aβ) proteins is of significant importance to the diagnosis of Alzheimer's disease (AD). In the paper, we prepared two new NIR probes, NIR-1 and NIR-2, through hydrophilic modification of introducing water-soluble bioactive groups such as polyethylene glycol (PEG) and morpholine to tune in vivo pharmacokinetics for specific detection of soluble and insoluble Aβ species. The in vitro assessments confirm that both NIR-1 and NIR-2 display strong near-infrared (NIR) fluorescence (FL) enhancement upon association with Aβ42 monomers, oligomers or aggregates (λem > 670 nm) and show high sensitive, rapid and selective response towards Aβ42 species. After i.v. injection, each probe showed fast blood-brain barrier (BBB) penetration and immediately produced intense FL signals in the brain of APP/PS1 AD model mice at 10 min. Moreover, compared with NIR-2, NIR-1 bearing hydrophilic PEG chain displayed not only more rapid clearance but also lower background signal to efficiently distinguish APP/PS1 mice and wild-type mice with higher signal-to-background ratio, which was further validated by ex vivo histological staining of brain tissues. Therefore, due to its excellent pharmacokinetics, NIR-1 shows great promise as an effective NIR probe for specific detection of Aβ species.

Hybrid Membrane Biomimetic Photothermal Nanorobots for Enhanced Chemodynamic-Chemotherapy-Immunotherapy.

Glioblastoma multiforme (GBM) is a highly invasive and fatal brain tumor with a grim prognosis, where current treatment modalities, including postoperative radiotherapy and temozolomide chemotherapy, yield a median survival of only 15 months. The challenges of tumor heterogeneity, drug resistance, and the blood-brain barrier necessitate innovative therapeutic approaches. This study introduces a strategy employing biomimetic magnetic nanorobots encapsulated with hybrid membranes derived from platelets and M1 macrophages to enhance blood-brain barrier penetration and target GBM. The nanorobots encapsulate a polypyrrole/Fe3O4 nanocomplex (PPy@F) for photothermal therapy (PTT) and promote the Fenton reaction of Fe3O4 to generate chemodynamic therapy (CDT). Additionally, temozolomide and PD-L1 antibody (SNTSESF) act as chemotherapy drug and immune checkpoint inhibitor, respectively. The biomimetic design leverages the functional properties of cell membranes to improve the blood residence time and tumor targeting. The integration of PTT and CDT aims to transform "cold" tumors into "hot" tumors, thereby enhancing immunotherapeutic efficacy. This multifaceted approach, PTT, CT, CDT, and immune checkpoint blockade therapy, offers a promising strategy for the treatment of GBM.

Targeting Soluble Amyloid Oligomers in Alzheimer's Disease: A Hypothetical Model Study Comparing Intrathecal Pseudodelivery of mAbs Against Intravenous Administration.

Neurotoxic soluble amyloid-β (Aβ) oligomers are key drivers of Alzheimer's pathology, with evidence suggesting that early targeting of these soluble forms may slow disease progression. Traditional intravenous (IV) monoclonal antibodies (mAbs) face challenges, including limited brain penetration and risks such as amyloid-related imaging abnormalities (ARIA). This hypothetical study aimed to model amyloid dynamics in early-to-moderate Alzheimer's disease (AD) and compare the efficacy of IV mAn with intrathecal pseudodelivery, a novel method that confines mAbs in a subcutaneous reservoir for selective amyloid clearance in cerebrospinal fluid (CSF) without systemic exposure. A mathematical framework was employed to simulate Aβ dynamics in patients with early-to-moderate AD. Two therapeutic approaches were compared: IV mAb and intrathecal pseudodelivery of mAb. The model incorporated amyloid kinetics, mAb affinity, protofibril size, and therapy-induced clearance rates to evaluate the impact of both methods on amyloid reduction, PET negativity timelines, and the risk of ARIA. Intrathecal pseudodelivery significantly accelerated Aβ clearance compared to IV administration, achieving amyloid PET scan negativity by month 132, as opposed to month 150 with IV mAb. This method demonstrated no ARIA risk and reduced amyloid reaccumulation. By targeting soluble Aβ species more effectively, intrathecal pseudodelivery emerged as a safer and more efficient strategy for early AD intervention. Intrathecal pseudodelivery offers a promising alternative to IV mAbs, overcoming challenges associated with blood-brain barrier penetration and systemic side effects. Further research should focus on optimizing this approach and exploring combination therapies to enhance clinical outcomes in AD.

Size effect-based improved antioxidant activity of selenium nanoparticles regulating Anti-PI3K-mTOR and Ras-MEK pathways for treating spinal cord injury to avoid hormone shock-induced immunosuppression

Spinal cord injury (SCI) is a critical condition affecting the central nervous system that often has permanent and debilitating consequences, including secondary injuries. Oxidative damage and inflammation are critical factors in secondary pathological processes. Selenium nanoparticles have demonstrated significant antioxidative and anti-inflammatory properties via a non-immunosuppressive pathway; however, their clinical application has been limited by their inadequate stability and functionality to cross the blood-spinal cord barrier (BSCB). This study proposed a synthesis method for ultra-small-diameter lentinan Se nanoparticles (LNT-UsSeNPs) with significantly superior reactive oxygen species (ROS) scavenging capabilities compared to conventional lentinan Se nanoparticles (LNT-SeNPs). These compounds effectively protected PC-12 cells from oxidative stress-induced cytotoxicity, alleviated mitochondrial dysfunction, reduced apoptosis. In vivo studies indicated that LNT-UsSeNPs efficiently penetrated the BSCB and effectively inhibited the apoptosis of spinal neurons. Ultimately, LNT-UsSeNPs directly regulated the PI3K-AKT-mTOR and Ras-Raf-MEK-ERK signaling pathways by regulating selenoproteins to achieve non-immunosuppressive anti-inflammatory therapy. Owing to their ultra-small size, LNT-UsSeNPs exhibited strong spinal barrier penetration and potent antioxidative and anti-inflammatory effects without compromising immune function. These findings suggest that LNT-UsSeNPs are promising candidates for further development in nanomedicine for the effective treatment of SCI.Graphical abstract

Observation of Large Low-Field Magnetoresistance in Layered (NdNiO3)n:NdO Films at High Temperatures.

Large low-field magnetoresistance (LFMR, <1 T), related to the spin-disorder scattering or spin-polarized tunneling at boundaries of polycrystalline manganates, holds considerable promise for the development of low-power and ultrafast magnetic devices. However, achieving significant LFMRtypically necessitates extremely low temperatures due to diminishing spin polarization as temperature rises. To address this challenge, one strategy involves incorporating Ruddlesden-Popper structures (ABO3)n:AO, which are layered derivatives of perovskite structure capable of potentially inducing heightened magnetic fluctuations at higher temperatures. Here, a remarkable LFMR of up to 1.0×103% is obtained in the layered (NdNiO3)n:NdO films with a high and wide temperature range (190-240 K). This finding underlines that the layered (NdNiO3)n:NdO (n = 1) structure show a complex magnetic structure above TMI of perovskite NdNiO3, where small ferromagnetic domains are embedded in the antiferromagnetic domains, raising the tunneling barriers and magnetic fluctuations at high temperatures. Furthermore, applying a low magnetic field (<0.1 T) near TMI effectively mitigates the disruption of antiferromagnetic order structures at boundaries, then a higher temperature is required to break the inhibition of ferromagnetic to antiferromagnetic phase transition. The results contribute significantly to the advancement of magnetic devices capable of achieving substantial LFMR at room temperature.

Enormous Out-of-Plane Charge Rectification and Conductance through Two-Dimensional Monolayers.

Heterogeneous integration of emerging two-dimensional (2D) materials with mature three-dimensional (3D) silicon-based semiconductor technology presents a promising approach for the future development of energy-efficient, function-rich nanoelectronic devices. In this study, we designed a mixed-dimensional junction structure in which a 2D monolayer (e.g., graphene, MoS2, and h-BN) is sandwiched between a metal (e.g., Ti, Au, and Pd) and a 3D semiconductor (e.g., p-Si) to investigate charge transport properties exclusively in an out-of-plane (OoP) direction. The role of 2D monolayers as either an OoP metal-to-semiconductor charge injection barrier or an OoP semiconductor-to-metal charge collection barrier was comparatively evaluated. Compared to monolayer graphene, monolayer MoS2 and h-BN effectively modulate OoP metal-to-semiconductor charge injection through a barrier tunneling effect. Their effective OoP resistance and resistivity were extracted using a resistors-in-series model. Intriguingly, when functioning as a semiconductor-to-metal charge collection barrier, all 2D monolayers become electronically "transparent" (close to zero resistance) when a high OoP voltage (greater than the built-in voltage) is applied. As a mixed-dimensional integrated diode, the Ti/MoS2/p-Si and Au/MoS2/p-Si configurations exhibit both high OoP rectification ratios (5.4 × 104) and conductance (1.3 × 105 S/m2). Our work demonstrates the tunable OoP charge transport characteristics at a 2D/3D interface, suggesting the opportunity for 2D/3D heterogeneous integration, even with sub-1 nm thick 2D monolayers, to enhance modern Si-based electronic devices.

Anti-inflammatory effects of moxifloxacin and levofloxacin on cadmium-activated human astrocytes: Inhibition of proinflammatory cytokine release, TLR4/STAT3, and ERK/NF-κB signaling pathway.

Cadmium is a non-essential element and neurotoxin that causes neuroinflammation, which leads to neurodegenerative diseases and brain cancer. To date, there are no specific or effective therapeutic agents to control inflammation and alleviate cadmium-induced progressive destruction of brain cells. Fluoroquinolones (FQs), widely used antimicrobials with effective blood-brain barrier penetration, show promise in being repurposed as anti-inflammatory drugs. Therefore, we aimed to test the efficacy of repurposed FQs for the treatment of cadmium-induced inflammation using cultures of U-87 MG human astrocytes and primary human astrocytes. Both FQs abrogated cadmium-induced interleukin (IL)-6 and IL-8 release from human astrocytes in a concentration and time-dependent manner, although levofloxacin had a stronger inhibitory effect than moxifloxacin. The downregulation of inflammatory cytokine release occurred with a concomitant reduction in cadmium-induced elevations in p65 nuclear factor-κB (NF-κB) and extracellular signal-regulated kinases (ERKs) 1/2 phosphorylation. Additionally, levofloxacin treatment significantly alleviated cadmium-induced activation of phosphorylated NF-κB translocation and toll-like receptor (TLR)-4/signal transducer and activator of transcription (STAT) 3 signaling. Transcriptome analysis revealed that modulation of inflammation-related pathways was the most enriched after FQ treatment. Our data suggest that FQs, particularly levofloxacin, attenuate the inflammatory process mediated by cadmium in human astrocytes. These effects may be mediated, at least in part, by inhibition of immune pathways regulated by TLR4, STAT3, ERK MAPK, and NF-κB.

Improving natural red pigment production by Streptomyces phaeolivaceus strain GH27 for functionalization of textiles with in silico ADME prediction

The red pigment was recovered from the S. phaeolivaceus GH27 isolate, which was molecularly identified using 16S rRNA gene sequencing and submitted to GenBank as OQ145635.1. The ideal growth conditions included 1% (w/v) starch, diammonium citrate, dibasic sodium phosphate, 5% (v/v) inoculum, pH 8, a rotation speed of 150 rpm, a temperature of 37 °C, and an incubation period of 9 days. Using ethanol as a solvent, the red pigment was effectively recovered. Data indicates that pigment content remained steady at 40 and 50 °C. Heating the pigment extract to 60, 70, 80, 90, and 100 °C for one hour results in pigment retention of 98%, 96.5%, 95.5%, 94.6%, and 92.6% of its pigment density, respectively. Studies indicate that the pigment extracts exhibited optimal stability at alkaline pH levels. The findings demonstrate that the red pigment extract has a peak absorbance range of 280–340 nm, with a λmax of 300 nm. GC/MS analysis revealed that the primary components of the pigment extract were linolenic acid methyl ester and oleic acid methyl ester, constituting 26.41% and 25.25%, respectively. Fabrics dyed with extracted red pigment exhibit excellent fastness when using the comprehensive green method. In comparison to conventional and nanotechnological attributes, printed samples exhibit significant color strength without environmental repercussions. The treatment of cotton, wool, and polyester samples suppressed pathogen growth to differing extents. Polyester had the most important inhibitory effects on Staphylococcus aureus (50.03%) and Bacillus cereus (39.49%). The ADME physicochemical properties of the predominant medication were assessed, together with its bioavailability. The radar plot demonstrated ideal parameters for size, polarity, lipophilicity, solubility, and saturation, excluding flexibility. It exhibited intermediate synthetic accessibility, exceptional permeability and absorption, elevated gastrointestinal absorption, and blood–brain barrier penetration; nonetheless, it did not adhere to the medicinal chemistry rule of three.Graphical

An Integrative Computational Approach for the Identification of C-Abl Kinase Inhibitors from Anti-Parkinson Plant-Derived Bioactive.

Oxidative stress is strongly linked to neurodegeneration through the activation of c-Abl kinase, which arrests α-synuclein proteolysis by interacting with parkin interacting substrate (PARIS) and aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2). This activation, triggered by ataxia-telangiectasia mutated (ATM) kinase, leads to dopaminergic neuron loss and α-synuclein aggregation, a critical pathophysiological aspect of Parkinson's disease (PD). To halt PD progression, pharmacological inhibition of c-Abl kinase is essential. Despite three generations of tyrosine kinase inhibitors (TKIs) being explored for PD treatment, they present significant concerns including poor blood-brain barrier penetration, off-target effects, and severe side effects. Notably, there are currently no FDA-approved c-Abl kinase inhibitors in clinical usage for PD treatment, highlighting the urgent need for potent, safe, and cost-effective alternatives. This study aims to identify potential c-Abl kinase inhibitors from plant-derived compounds with reported anti-Parkinson's potential and their derivatives using molecular docking, molecular dynamics simulations (MDS), and in silico pharmacokinetics and toxicity profiling. Seventy-eight compounds sourced from literature were docked against c-Abl kinase using Maestro 12.5. The top three hit compounds, along with nilotinib (control drug), were subjected to drug-likeness, ADMET profiling using the AI Drug Lab server and 100 ns MDS using Desmond. Amburoside A, diarylheptanoid MS13, and dimethylaminomethyl-substituted-curcumin showed binding affinities close to nilotinib, with values of -12.615, -12.556, and -11.895 kcal/mol respectively, compared to nilotinib's -16.826 kcal/mol. The three plant-derived compounds exhibited excellent structural stability and favorable ADMET profiles, including optimal blood-brain barrier permeation Conclusion: The three hit compounds identified in this study show potential as c-Abl kinase inhibitors. Given the absence of FDA-approved c-Abl kinase inhibitors for PD, these findings are significant as they could contribute new therapeutic options for the treatment and management of PD. However, further in vitro and in vivo experiments are necessary to validate these findings.

First-Principles Assessment of ZnTe and CdSe as Prospective Tunnel Barriers at the InAs/Al Interface.

Majorana zero modes are predicted to emerge in semiconductor/superconductor interfaces, such as InAs/Al. Majorana modes could be utilized for fault tolerant topological qubits. However, their realization is hindered by materials challenges. The coupling between the superconductor and the semiconductor may be too strong for Majorana modes to emerge, due to effective doping of the semiconductor by the metallic contact. This could be mediated by adding a tunnel barrier of controlled thickness. We use density functional theory (DFT) with Hubbard U corrections, whose values are machine-learned via Bayesian optimization (BO), to assess ZnTe and CdSe as prospective tunnel barriers for the InAs/Al interface. The results of DFT+U(BO) for ZnTe are validated by comparison to angle resolved photoemission spectroscopy (ARPES). We then study bilayer interfaces of the three semiconductors with each other and with Al, as well as trilayer interfaces with a varying number of ZnTe or CdSe layers inserted between InAs and Al. We find that 16 atomic layers of either material completely insulate the InAs from metal induced gap states (MIGS). However, ZnTe and CdSe differ significantly in their band alignment, such that ZnTe forms an effective barrier for electrons, whereas CdSe forms a barrier for holes. Because of Fermi level pinning in the conduction band at the interface, only electron transport is relevant for InAs-based Majorana devices. Therefore, ZnTe is the better choice. Based on the results of our simulations, we suggest conducting experiments with ZnTe barriers in the thickness range of 6-18 atomic layers.

Bias voltage controlled inversions of tunneling magnetoresistance in van der Waals heterostructures Fe3GaTe2/hBN/Fe3GaTe2

Abstract We report the bias voltage-controlled inversions of tunnel magnetoresistance (TMR) in magnetic tunneling junctions composed of Fe3GaTe2 electrodes and hBN tunneling barrier, observed at room temperature. The polarity reversal of TMR occurs consistently at around 0.625 V across multiple devices and temperatures, highlighting the robustness of the effect. To understand this behavior, we developed a theoretical model incorporating spin-resolved density of states (DOS) at high energy levels. By adjusting the DOS weighting at different k-points to account for misalignment between the crystal structure of electrodes in experimental devices, we improved agreement between experimental and theoretical inversion voltages. Our results provide valuable insight into the voltage-controlled spin injection and detection in two-dimensional magnetic tunnel junctions, with implications for the development of energy-efficient spintronic devices.

Applications of polymeric nanoparticles in drug delivery for glioblastoma.

Glioblastoma (GBM) remains one of the most aggressive and treatment-resistant brain tumors, necessitating innovative therapeutic approaches. Polymer-based nanotechnology has emerged as a promising solution, offering precise drug delivery, enhanced blood-brain barrier (BBB) penetration, and adaptability to the tumor microenvironment (TME). This review explores the diverse applications of polymeric nanoparticles (NPs) in GBM treatment, including delivery of chemotherapeutics, targeted therapeutics, immunotherapeutics, and other agents for radiosensitization and photodynamic therapy. Recent advances in targeted delivery and multifunctional polymer highlight their potential to overcome the challenges that GBM brought, such as heterogeneity of the tumor, BBB limitation, immunosuppressive TME, and consideration of biocompatibility and safety. Meanwhile, the future directions to address these challenges are also proposed. By addressing these obstacles, polymer-based nanotechnology represents a transformative strategy for improving GBM treatment outcomes, paving the way for more effective and patient-specific therapies.

Magnetochiral charge pumping due to charge trapping and skin effect in chirality-induced spin selectivity

Chirality-induced spin selectivity (CISS) generates giant spin polarization in transport through chiral molecules, paving the way for novel spintronic devices and enantiomer separation. Unlike conventional transport, CISS magnetoresistance (MR) violates Onsager’s reciprocal relation, exhibiting significant resistance changes when reversing electrode magnetization at zero bias. However, its underlying mechanism remains unresolved. In this work, we propose that CISS MR originates from charge trapping that modifies the electron tunneling barrier and circumvents Onsager’s relation, distinct from previous spin polarization-based models. Charge trapping is governed by the non-Hermitian skin effect, where dissipation leads to exponential wavefunction localization at the ferromagnet-chiral molecule interface. Reversing magnetization or chirality alters the localization direction, changing the occupation of impurity/defect states in the molecule (i.e., charge trapping) – a phenomenon we term magnetochiral charge pumping. Our theory explains why CISS MR can far exceed the ferromagnet spin polarization and why chiral molecules violate the reciprocal relation but chiral metals do not. Furthermore, it predicts exotic phenomena beyond the conventional CISS framework, including asymmetric MR induced by magnetic fields alone (without ferromagnetic electrodes), as confirmed by recent experiments. This work offers a deeper understanding of CISS and opens avenues for controlling electrostatic interactions in chemical and biological systems through the magnetochiral charge pumping.

Tunnel barriers for Fe-based spin valves providing high spin-polarized current.

Employing density functional theory for ground state quantum mechanical calculations and the non-equilibrium Green's function method for transport calculations, we investigate the potential of CdS, ZnS, Cd3ZnS4, and Zn3CdS4 as tunnel barriers in magnetic tunnel junctions for spintronics. Based on the finding that the valence band edges of these semiconductors are dominated by pz orbitals and the conduction band edges by s orbitals, we show that Δ1 symmetry filtering of the Bloch states in magnetic tunnel junctions with Fe electrodes results in high tunneling magnetoresistances and high spin-polarized current (up to two orders of magnitude higher than in the case of the Fe/MgO/Fe magnetic tunnel junction).

Synthesis, Antileishmanial Activity, and in silico Study of 2-Hydroxy-3-(1,2,3-triazolyl)propyl Vanillin Derivatives

This study details the preparation, antileishmanial assay, and in silico analysis of twenty 2-hydroxy-3-(1,2,3-triazolyl)propyl vanillin derivatives. These compounds were synthesized in three steps and evaluated against Leishmania infantum, Leishmania amazonensis, and Leishmania braziliensis promastigotes. Compounds 3s and 3t were the most effective, showing good activity against all Leishmania species tested. Molecular docking indicated that all compounds bind favorably to the sterol 14α-demethylase (CYP51) enzyme from L. infantum. ADMET (absorption, distribution, metabolism, excretion and toxicity) analysis indicated good oral bioavailability, non-blood-brain barrier penetration, and high gastrointestinal absorption. Posaconazole and compounds 3e, 3s, and 3t remained stable in the CYP51 binding region during 100 ns molecular dynamics (MD) simulations. Root mean square deviation (RMSD) and root mean square fluctuations (RMSF) analyses from the MD trajectory revealed significant conformational fluctuations of the CYP51 N-terminal, suggesting occasional expulsion of 3e, potentially explaining its higher IC50 (half-maximal inhibitory concentration) values. Pairwise decomposition analyses from molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations highlighted the importance of hydrophobic residues in interacting with the synthesized derivatives.

Inhibition of monoamine oxidases by heterocyclic derived conjugated dienones: synthesis and in vitro and in silico investigations.

A total of 18 heterocyclic derived conjugated dienones (CD1-CD18) were evaluated for their potential monoamine oxidase (MAO)-A/-B inhibitory activity. Among the analyzed molecules, CD11 and CD14 showed notable inhibitory potentials against MAO-B, with half-maximal inhibitory concentration (IC50) values of 0.063 ± 0.001 μM and 0.036 ± 0.008 μM, respectively. In contrast, CD1, CD2 and CD3 showed comparable inhibitory activities toward MAO-A, with IC50 values of 3.45 ± 0.07, 3.23 ± 0.24, and 3.15 ± 0.10 μM, respectively. Derivatives of thiophene (CD13-CD17) exhibited selectivity indices greater than 250 for MAO-B. Both lead compounds exhibited similar potencies to safinamide and were more potent than pargyline. According to kinetic analysis, CD11 and CD14 exhibited competitive inhibition of MAO-B activity, with K i values of 12.67 ± 3.85 nM and 4.5 ± 0.62 nM, respectively. Furthermore, the reversibility test results indicated that the inhibitions were reversible. Molecular docking and molecular dynamics simulation studies can provide insights into the probable binding interactions of CD11 and CD14 with MAO-B. CD11 demonstrated a bipartite contact with Tyr326 and Phe343, whereas CD14 showed contact with Pro102 and Tyr435 via aromatic hydrogen bonds. These results indicated that both compounds have high-affinity binding interactions ( -10.13 and -9.90 kcal mol-1, respectively) at the active site of MAO-B. Furthermore, we used SwissADME to estimate ADME, and both lead compounds demonstrated blood-brain barrier penetration. The study results indicated that all the compounds evaluated demonstrated potent inhibition of MAO-B activity, which was comparable to the efficacy of reference medications. It is necessary to do further investigations on the lead molecules to see whether they may be used to treat different neurodegenerative illnesses.

Advancing neurological disorders therapies: Organic nanoparticles as a key to blood-brain barrier penetration.

The blood-brain barrier (BBB) plays a vital role in protecting the central nervous system (CNS) by preventing the entry of harmful pathogens from the bloodstream. However, this barrier also presents a significant obstacle when it comes to delivering drugs for the treatment of neurodegenerative diseases and brain cancer. Recent breakthroughs in nanotechnology have paved the way for the creation of a wide range of nanoparticles (NPs) that can serve as carriers for diagnosis and therapy. Regarding their promising properties, organic NPs have the potential to be used as effective carriers for drug delivery across the BBB based on recent advancements. These remarkable NPs have the ability to penetrate the BBB using various mechanisms. This review offers a comprehensive examination of the intricate structure and distinct properties of the BBB, emphasizing its crucial function in preserving brain balance and regulating the transport of ions and molecules. The disruption of the BBB in conditions such as stroke, Alzheimer's disease, and Parkinson's disease highlights the importance of developing creative approaches for delivering drugs. Through the encapsulation of therapeutic molecules and the precise targeting of transport processes in the brain vasculature, organic NP formulations present a hopeful strategy to improve drug transport across the BBB. We explore the changes in properties of the BBB in various pathological conditions and investigate the factors that affect the successful delivery of organic NPs into the brain. In addition, we explore the most promising delivery systems associated with NPs that have shown positive results in treating neurodegenerative and ischemic disorders. This review opens up new possibilities for nanotechnology-based therapies in cerebral diseases.

Tunneling barriers in an extended Marcus theory of electron transfer: Incorporating effects of the bridging medium.

The Marcus semi-classical and quantum theories of electron transfer (ET) have been extensively used to understand and predict tunneling ET reaction rates in the condensed phase. Previously, the traditional Marcus two-state model has been extended to a three-state model, which assumes a harmonic dependence of donor (D), bridge (B), and acceptor (A) free energies on the reaction (e.g., solvent polarization) coordinate. Here, we generalize the previously proposed three-state extended Marcus model (EMM) to an (N + 2)-state model for N bridge sites separating the D from the A. Using the EMM, an analytic expression for the electron tunneling barrier is derived. The EMM model predicts that both the relative thermodynamics of the D-A states and B state reorganization energies can influence the D-A electronic coupling. We discuss signatures of bridge state thermal fluctuations using the EMM on the driving force and distance dependence of ET rates, which can be tested experimentally.